Biliary penetration and pharmacodynamic exposure of linezolid in liver transplant patients.
OBJECTIVE
The aim of the study was to assess the biliary penetration of linezolid and the probabilities of attaining optimal pharmacodynamic exposure against vancomycin-resistant enterococci (VRE) in the bile of liver transplant (LTx) patients who received linezolid for the treatment of multidrug-resistant Gram-positive hospital infections.


METHODS
After at least 2 days of standard 600 mg twice-daily therapy, simultaneous bile and blood samples for linezolid assay were collected from six LTx patients just prior to drug administration to determine trough concentrations (Cmin) at steady-state in both sites. Linezolid concentrations in plasma and in bile were analysed by means of HPLC. Biliary penetration of linezolid was calculated as the ratio between Cmin in bile and in plasma. Optimal theoretical pharmacodynamic exposure of linezolid against VRE in bile was defined as biliary Cmin>MIC90.


RESULTS
C(min) of linezolid in bile achieved very high values at steady-state, which were significantly higher than in plasma (median of 21.77 versus 8.08 mg/L, P=0.021). The very high biliary penetration of linezolid (median value of 1.93; range 1.31-4.83) enabled achievement of optimal theoretical pharmacodynamic exposure against VRE in bile (Cmin>2 mg/L) on all of the occasions.


CONCLUSIONS
These preliminary data suggest a potential role for linezolid in the treatment of cholangitis due to VRE in LTx patients. Obviously, further confirmatory data assessing also the AUC/MIC ratio of linezolid in bile are needed.
Pea
Federico
F
Institute of Clinical Pharmacology and Toxicology, Department of Experimental and Clinical Pathology and Medicine, Medical School, University of Udine, Udine, Italy. pea.federico@aoud.sanita.fvg.it
Viale
Pierluigi
P
Lugano
Manuela
M
Baccarani
Umberto
U
Pavan
Federica
F
Tavio
Marcello
M
Adani
Gian Luigi
GL
Della Rocca
Giorgio
G
Furlanut
Mario
M
D000081:Acetamides / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001652:Bile Ducts / Q000737:chemistry*; D002761:Cholangitis / Q000188:drug therapy; D002851:Chromatography, High Pressure Liquid; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy; D006801:Humans; D000069349:Linezolid; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D023303:Oxazolidinones / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D010949:Plasma / Q000737:chemistry; D020713:Vancomycin Resistance
D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid